Medical research (or biomedical research ), also known as health research , refers to the process of using scientific methods with the aim to produce knowledge about human diseases, the prevention and treatment of illness, and the promotion of health.
122-645: The Australian Regenerative Medicine Institute ( ARMI ) is an Australian medical research institute . Opened in April 2009, the institute is based at the Clayton campus of Monash University , in the Monash Science Technology Research and Innovation Precinct . ARMI is one of the world's largest regenerative medicine and stem cell research hubs. Its research aims to restore and regenerate damaged tissue and organs by injecting or implanting cells to allow
244-425: A 7.8% increase (adjusted for inflation). In 2007 the most heavily funded institutions received 20% of HIN medical research funding, and the top 50 institutions received 58% of NIH medical research funding, the percent of funding allocated to the largest institutions is a trend which has increased only slightly over data from 1994. Relative to federal and private funding, health policy and service research accounted for
366-565: A US regulatory standpoint where great investment has been made in research ethics and standards, yet trial results remain inconsistent. Federal agencies have called upon greater regulation to address these problems; a spokesman from the National Institute of Neurological Disorders and Stroke, an agency of the NIH, stated that there is "widespread poor reporting of experimental design in articles and grant applications, that animal research should follow
488-434: A climate of secrecy and self-protection, stifling creativity and collaboration. The power imbalance in academic hierarchies exacerbates these issues, with junior researchers often subjected to exploitative practices and denied proper recognition for their contributions. After clinical research, medical therapies are typically commercialized by private companies such as pharmaceutical companies or medical device company. In
610-692: A conflict of interest in the field of biomedical research. Survey results from one study concluded that 43% of scientific investigators employed by a participating academic institution had received research related gifts and discretionary funds from industry sponsors. Another participating institution surveyed showed that 7.6% of investigators were financially tied to research sponsors, including paid speaking engagements (34%), consulting arrangements (33%), advisory board positions (32%) and equity (14%). A 1994 study concluded that 58% out of 210 life science companies indicated that investigators were required to withhold information pertaining to their research as to extend
732-616: A core set of research parameters, and that a concerted effort by all stakeholders is needed to disseminate best reporting practices and put them into practice". Medical research is highly regulated. National regulatory authorities are appointed in most countries to oversee and monitor medical research, such as for the development and distribution of new drugs. In the United States, the Food and Drug Administration oversees new drug development; in Europe,
854-454: A decline in the share of key research grants going to younger scientists, as well as a steady rise in the age at which investigators receive their first funding. A significant flaw in biomedical research is the toxic culture that particularly impacts medical students and early career researchers. They face challenges such as bullying, harassment, and unethical authorship practices. Intense competition for funding and publication pressures fosters
976-407: A doubling of NIH funding, spurring an era of great scientific progress. There have been dramatic changes in the era since the turn of the 21st century to date; roughly around the start of the century, the cost of trials dramatically increased while the rate of scientific discoveries did not keep pace. Biomedical research spending increased substantially faster than GDP growth over the past decade in
1098-402: A drug is brought to the market. The Kefauver-Harris amendments were met with opposition from industry due to the requirement of lengthier clinical trial periods that would lessen the period of time in which the investor is able to see return on their money. In the pharmaceutical industry patents are typically granted for a 20-year period of time, and most patent applications are submitted during
1220-537: A few significantly enlarged motor neurons doing work previously performed by as many as four or five units: a single motor neuron that once controlled 200 muscle cells might control 800 to 1000 cells. Other mechanisms that occur during the rehabilitation phase, and contribute to muscle strength restoration, include myofiber hypertrophy – enlargement of muscle fibers through exercise and activity – and transformation of type II muscle fibers to type I muscle fibers . In addition to these physiological processes,
1342-464: A limited number of competitors. Another visible shift during the era was a shift in focus to late stage research trials; formerly dispersed, since 1994 an increasingly large portion of industry-sponsored research was late phase trials rather than early-experimental phases now accounting for the majority of industry sponsored research. This shift is attributable to a lower risk investment and a shorter development to market schedule. The low risk preference
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#17328510751841464-738: A live, attenuated virus. It was produced by the repeated passage of the virus through nonhuman cells at sub physiological temperatures. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of wild poliovirus infection and replication, but the vaccine strain is unable to replicate efficiently within nervous system tissue. A single dose of Sabin's trivalent OPV produces immunity to all three poliovirus serotypes in about 50 percent of recipients. Three doses of OPV produce protective antibody to all three poliovirus types in more than 95 percent of recipients. Human trials of Sabin's vaccine began in 1957, and in 1958, it
1586-447: A local inflammatory response . In most cases, this causes a self-limiting inflammation of the meninges , the layers of tissue surrounding the brain , which is known as nonparalytic aseptic meningitis. Penetration of the CNS provides no known benefit to the virus, and is quite possibly an incidental deviation of a normal gastrointestinal infection. The mechanisms by which poliovirus spreads to
1708-478: A major illness involving the CNS, which may be paralytic or nonparalytic. Adults are more likely to develop symptoms, including severe symptoms, than children. In most people with a normal immune system , a poliovirus infection is asymptomatic . In about 25% of cases, the infection produces minor symptoms which may include sore throat and low fever. These symptoms are temporary and full recovery occurs within one or two weeks. In about 1 percent of infections
1830-589: A member of the genus Enterovirus known as poliovirus (PV). This group of RNA viruses colonize the gastrointestinal tract – specifically the oropharynx and the intestine . Its structure is quite simple, composed of a single (+) sense RNA genome enclosed in a protein shell called a capsid . In addition to protecting the virus' genetic material, the capsid proteins enable poliovirus to infect certain types of cells. Three serotypes of poliovirus have been identified – wild poliovirus type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3) – each with
1952-458: A nominal amount of sponsored research; health policy and service research was funded $ 1.8 billion in 2003, which increased to $ 2.2 billion in 2008. Stagnant rates of investment from the US government over the past decade may be in part attributable to challenges that plague the field. To date, only two-thirds of published drug trial findings have results that can be re-produced, which raises concerns from
2074-444: A nutritious diet. Treatment of polio often requires long-term rehabilitation, including occupational therapy , physical therapy , braces, corrective shoes and, in some cases, orthopedic surgery . Portable ventilators may be required to support breathing. Historically, a noninvasive, negative-pressure ventilator, more commonly called an iron lung , was used to artificially maintain respiration during an acute polio infection until
2196-456: A permanent residual impairment after recovery from the acute illness, and both overuse and disuse of neurons. PPS is a slow, progressive disease, and there is no specific treatment for it. Post-polio syndrome is not an infectious process, and persons experiencing the syndrome do not shed poliovirus. Paralysis, length differences and deformations of the lower extremities can lead to a hindrance when walking with compensation mechanisms that lead to
2318-553: A person could breathe independently (generally about one to two weeks). The use of iron lungs is largely obsolete in modern medicine as more modern breathing therapies have been developed and due to the eradication of polio in most of the world. Other historical treatments for polio include hydrotherapy , electrotherapy , massage and passive motion exercises, and surgical treatments, such as tendon lengthening and nerve grafting. Patients with abortive polio infections recover completely. In those who develop only aseptic meningitis,
2440-608: A primary interest (such as a person's welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain)." Regulation on industry funded biomedical research has seen great changes since Samuel Hopkins Adams declaration. In 1906 congress passed the Pure Food and Drugs Act of 1906. In 1912 Congress passed the Shirley Amendment to prohibit the wide dissemination of false information on pharmaceuticals. The Food and Drug Administration
2562-487: A result of the Human Genome Project . Many challenges remain, however, including the appearance of antibiotic resistance and the obesity epidemic . Example areas in basic medical research include: cellular and molecular biology , medical genetics , immunology , neuroscience , and psychology . Researchers, mainly in universities or government-funded research institutes, aim to establish an understanding of
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#17328510751842684-736: A service. They can also help to make the research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for. Research funding in many countries derives from research bodies and private organizations which distribute money for equipment, salaries, and research expenses. United States, Europe, Asia, Canada, and Australia combined spent $ 265.0 billion in 2011, which reflected growth of 3.5% annually from $ 208.8 billion in 2004. The United States contributed 49% of governmental funding from these regions in 2011 compared to 57% in 2004. In
2806-457: A severe impairment of the gait pattern. In order to be able to stand and walk safely and to improve the gait pattern, orthotics can be included in the therapy concept. Today, modern materials and functional elements enable the orthosis to be specifically adapted to the requirements resulting from the patient's gait. Mechanical stance phase control knee joints may secure the knee joint in the early stance phases and release again for knee flexion when
2928-424: A slightly different capsid protein. All three are extremely virulent and produce the same disease symptoms. WPV1 is the most commonly encountered form, and the one most closely associated with paralysis. WPV2 was certified as eradicated in 2015 and WPV3 certified as eradicated in 2019. The incubation period (from exposure to the first signs and symptoms) ranges from three to six days for nonparalytic polio. If
3050-495: A slow development of muscle weakness similar to what the person had during the initial infection. Polio occurs naturally only in humans. It is highly infectious, and is spread from person to person either through fecal–oral transmission (e.g. poor hygiene, or by ingestion of food or water contaminated by human feces), or via the oral–oral route. Those who are infected may spread the disease for up to six weeks even if no symptoms are present. The disease may be diagnosed by finding
3172-401: A stark contrast in federal investment, from 1994 to 2003, federal funding increased 100% (adjusted for inflation). The NIH manages the majority, over 85%, of federal biomedical research expenditures. NIH support for biomedical research decreased from $ 31.8 billion in 2003, to $ 29.0 billion in 2007, a 25% decline (in real terms adjusted for inflation), while non-NIH federal funding allowed for
3294-798: A stark contrast to 25% increase in recent years. Of industry sponsored research, pharmaceutical firm spending was the greatest contributor from all industry sponsored biomedical research spending, but only increased 15% (adjusted for inflation) from 2003 to 2007, while device and biotechnology firms accounted for the majority of the spending. The stock performance, a measure that can be an indication of future firm growth or technological direction, has substantially increased for both predominantly medical device and biotechnology producers. Contributing factors to this growth are thought to be less rigorous FDA approval requirements for devices as opposed to drugs, lower cost of trials, lower pricing and profitability of products and predictable influence of new technology due to
3416-462: A type of monkey kidney tissue culture ( vero cell line ), which is chemically inactivated with formalin . After two doses of IPV (given by injection ), 90 percent or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99 percent are immune to poliovirus following three doses. Subsequently, Albert Sabin developed a polio vaccine that can be administered orally (oral polio vaccine - OPV), comprising
3538-508: A working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and complement their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using
3660-575: Is applied research , or translational research , conducted to expand knowledge in the field of medicine . Both clinical and preclinical research phases exist in the pharmaceutical industry 's drug development pipelines, where the clinical phase is denoted by the term clinical trial . However, only part of the clinical or preclinical research is oriented towards a specific pharmaceutical purpose. The need for fundamental and mechanism-based understanding, diagnostics , medical devices , and non-pharmaceutical therapies means that pharmaceutical research
3782-435: Is also reflected in the trend of large pharmaceutical firms acquiring smaller companies that hold patents to newly developed drug or device discoveries which have not yet passed federal regulation (large companies are mitigating their risk by purchasing technology created by smaller companies in early-phase high-risk studies). Medical research support from universities increased from $ 22 billion in 2003 to $ 27.7 billion in 2007,
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3904-472: Is an infectious disease caused by the poliovirus . Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe symptoms develop such as headache , neck stiffness, and paresthesia . These symptoms usually pass within one or two weeks. A less common symptom is permanent paralysis , and possible death in extreme cases. Years after recovery, post-polio syndrome may occur, with
4026-455: Is called respiratory or bulbospinal polio. Here, the virus affects the upper part of the cervical spinal cord ( cervical vertebrae C3 through C5), and paralysis of the diaphragm occurs. The critical nerves affected are the phrenic nerve (which drives the diaphragm to inflate the lungs ) and those that drive the muscles needed for swallowing. By destroying these nerves, this form of polio affects breathing, making it difficult or impossible for
4148-544: Is funded by industry can be considered valid after a 2003 publication of "Scope and Impact of Financial Conflicts of Interest in Biomedical Research" in The Journal of American Association of Medicine. This publication included 37 different studies that met specific criteria to determine whether or not an academic institution or scientific investigator funded by industry had engaged in behavior that could be deduced to be
4270-416: Is known as acute flaccid paralysis . The weakness most often involves the legs, but may less commonly involve the muscles of the head, neck, and diaphragm . Depending on the site of paralysis, paralytic poliomyelitis is classified as spinal, bulbar , or bulbospinal. In those who develop paralysis, between 2 and 10 percent die as the paralysis affects the breathing muscles. Encephalitis , an infection of
4392-413: Is less effective at preventing spread of wild poliovirus by the fecal–oral route. Because the oral polio vaccine is inexpensive, easy to administer, and produces excellent immunity in the intestine (which helps prevent infection with wild virus in areas where it is endemic ), it has been the vaccine of choice for controlling poliomyelitis in many countries. On very rare occasions, the attenuated virus in
4514-483: Is managed and made publicly available on usaspending.gov. Aside from the main source, usaspending.gov, other reporting mechanisms exist: Data specifically on biomedical research funding from federal sources is made publicly available by the National Health Expenditure Accounts (NHEA), data on health services research, approximately 0.1% of federal funding on biomedical research, is available through
4636-416: Is most infectious between 7 and 10 days before and after the appearance of symptoms, but transmission is possible as long as the virus remains in the saliva or feces. Virus particles can be excreted in the feces for up to six weeks. Factors that increase the risk of polio infection include pregnancy , the very old and the very young, immune deficiency , and malnutrition . Although the virus can cross
4758-513: Is only a small part of medical research. Most of the research in the field is pursued by biomedical scientists , but significant contributions are made by other type of biologists . Medical research on humans has to strictly follow the medical ethics sanctioned in the Declaration of Helsinki and the institutional review board where the research is conducted. In all cases, research ethics are expected. The increased longevity of humans over
4880-420: Is possible up to 18 months after infection. One mechanism involved in recovery is nerve terminal sprouting, in which remaining brainstem and spinal cord motor neurons develop new branches, or axonal sprouts. These sprouts can reinnervate orphaned muscle fibers that have been denervated by acute polio infection, restoring the fibers' capacity to contract and improving strength. Terminal sprouting may generate
5002-403: Is that of which industry is the financier for academic institutions which in turn employ scientific investigators to conduct research. A fear that exists wherein a project is funded by industry is that firms might negate informing the public of negative effects to better promote their product. A list of studies shows that public fear of the conflicts of interest that exist when biomedical research
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5124-430: Is that one leg is shorter than the other and the person limps and leans to one side, in turn leading to deformities of the spine (such as scoliosis ). Osteoporosis and increased likelihood of bone fractures may occur. An intervention to prevent or lessen length disparity can be to perform an epiphysiodesis on the distal femoral and proximal tibial/fibular condyles, so that limb's growth is artificially stunted, and by
5246-443: Is usually complete by the time the fever breaks. The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases. In children under five years of age, paralysis of one leg is most common; in adults, extensive paralysis of
5368-463: Is usually made based on the recovery of poliovirus from a stool sample or a swab of the pharynx . Rarely, it may be possible to identify poliovirus in the blood or in the cerebrospinal fluid . Poliovirus samples are further analysed using reverse transcription polymerase chain reaction (RT-PCR) or genomic sequencing to determine the serotype (i.e., 1, 2, or 3), and whether the virus is a wild or vaccine-derived strain. In 1950, William Hammon at
5490-597: The Bill and Melinda Gates Foundation , contributed about 3% of the funding. These funders are attempting to maximize their return on investment in public health . One method proposed to maximize the return on investment in medicine is to fund the development of open source hardware for medical research and treatment. The enactment of orphan drug legislation in some countries has increased funding available to develop drugs meant to treat rare conditions, resulting in breakthroughs that previously were uneconomical to pursue. Since
5612-601: The European Medicines Agency (see also EudraLex ); and in Japan , the Ministry of Health, Labour and Welfare . The World Medical Association develops the ethical standards for medical professionals involved in medical research. The most fundamental of them is the Declaration of Helsinki . The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) works on
5734-601: The European Molecular Biology Laboratory and Harvard Medical School . Professor Peter Currie was appointed Director in February 2016, following Rosenthal's return to the US. In 2014, the Currie group (with collaborators) published research describing the process of hematopoietic stem cell (HSC) formation in zebrafish , furthering efforts to produce HSCs in vitro . As of December 2023, there are 15 groups at
5856-523: The Southern Hemisphere . The institute was established through an A$ 153 million joint venture between Monash University and the Victorian Government to deliver the next generation of discoveries in regenerative medicine. The Australian Regenerative Medicine Institute officially opened in April 2009. Its foundation director was Professor Nadia Rosenthal . Rosenthal has previously served at
5978-681: The United Kingdom , funding bodies such as the National Institute for Health and Care Research (NIHR) and the Medical Research Council derive their assets from UK tax payers, and distribute revenues to institutions by competitive research grants . The Wellcome Trust is the UK's largest non-governmental source of funds for biomedical research and provides over £600 million per year in grants to scientists and funds for research centres. In
6100-458: The University of Pittsburgh purified the gamma globulin component of the blood plasma of polio survivors. Hammon proposed the gamma globulin, which contained antibodies to poliovirus, could be used to halt poliovirus infection, prevent disease, and reduce the severity of disease in other patients who had contracted polio. The results of a large clinical trial were promising; the gamma globulin
6222-422: The chest and abdomen also affecting all four limbs – quadriplegia – is more likely. Paralysis rates also vary depending on the serotype of the infecting poliovirus; the highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one in 2,000) are associated with type 2. Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of
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#17328510751846344-421: The cranial nerves , producing symptoms of encephalitis , and causes difficulty breathing , speaking and swallowing. Critical nerves affected are the glossopharyngeal nerve (which partially controls swallowing and functions in the throat, tongue movement, and taste), the vagus nerve (which sends signals to the heart, intestines, and lungs), and the accessory nerve (which controls upper neck movement). Due to
6466-431: The experimental subjects . It is generally supervised by physicians and conducted by nurses in a medical setting, such as a hospital or research clinic, and requires ethical approval. Besides being participants in a clinical trial, members of the public can actively collaborate with researchers in designing and conducting medical research. This is known as patient and public involvement (PPI). Public involvement involves
6588-411: The maternal-fetal barrier during pregnancy, the fetus does not appear to be affected by either maternal infection or polio vaccination. Maternal antibodies also cross the placenta , providing passive immunity that protects the infant from polio infection during the first few months of life. Poliovirus enters the body through the mouth, infecting the first cells with which it comes in contact –
6710-422: The pharynx and intestinal mucosa . It gains entry by binding to an immunoglobulin-like receptor, known as the poliovirus receptor or CD155 , on the cell membrane. The virus then hijacks the host cell's own machinery, and begins to replicate . Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the tonsils (specifically the follicular dendritic cells residing within
6832-467: The polio vaccine , with multiple doses required for lifelong protection. There are two broad types of polio vaccine; an injected polio vaccine (IPV) using inactivated poliovirus and an oral polio vaccine (OPV) containing attenuated (weakened) live virus. Through the use of both types of vaccine, incidence of wild polio has decreased from an estimated 350,000 cases in 1988 to 30 confirmed cases in 2022, confined to just three countries. In rare cases,
6954-399: The CNS are poorly understood, but it appears to be primarily a chance event – largely independent of the age, gender, or socioeconomic position of the individual. In around one percent of infections, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within the spinal cord , brain stem , or motor cortex . This leads to
7076-803: The Coalition of Health Services Research, the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, the Centers for Medicare & Medicaid Services, and the Veterans Health Administration. Currently, there are not any funding reporting requirements for industry sponsored research, but there has been voluntary movement toward this goal. In 2014, major pharmaceutical stakeholders such as Roche and Johnson and Johnson have made financial information publicly available and Pharmaceutical Research and Manufacturers of America (PhRMA),
7198-564: The FDA remained stagnant over the same time span. Financial projections indicate federal spending will remain constant in the near future. The National Institutes of Health (NIH) is the agency that is responsible for management of the lion's share of federal funding of biomedical research. It funds over 280 areas directly related to health. Over the past century there were two notable periods of NIH support. From 1995 to 1996 funding increased from $ 8.877 billion to $ 9.366 billion, years which represented
7320-557: The Sabin OPV can revert into a form that can paralyze. In 2017, cases caused by vaccine-derived poliovirus (cVDPV) outnumbered wild poliovirus cases for the first time, due to wild polio cases hitting record lows. Most industrialized countries have switched to inactivated polio vaccine, which cannot revert, either as the sole vaccine against poliomyelitis or in combination with oral polio vaccine. An improved oral vaccine (Novel oral polio vaccine type 2 - nOPV2) began development in 2011 and
7442-400: The US has seen great movement over the years. The 1980 Bayh–Dole Act was passed by Congress to foster a more constructive relationship between the collaboration of government and industry funded biomedical research. The Bayh Doyle Act gave private corporations the option of applying for government funded grants for biomedical research which in turn allowed the private corporations to license
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#17328510751847564-430: The US, between the years of 2003 and 2007 spending increased 14% per year, while GDP growth increased 1% over the same period (both measures adjusted for inflation). Industry, not-for-profit entities, state and federal funding spending combined accounted for an increase in funding from $ 75.5 billion in 2003 to $ 101.1 billion in 2007. Due to the immediacy of federal financing priorities and stagnant corporate spending during
7686-676: The United States, data from ongoing surveys by the National Science Foundation (NSF) show that federal agencies provided only 44% of the $ 86 billion spent on basic research in 2015. The National Institutes of Health and pharmaceutical companies collectively contribute $ 26.4 billion and $ 27 billion, which constitute 28% and 29% of the total, respectively. Other significant contributors include biotechnology companies ($ 17.9 billion, 19% of total), medical device companies ($ 9.2 billion, 10% of total), other federal sources, and state and local governments. Foundations and charities, led by
7808-533: The United States, one estimate found that in 2011, one-third of Medicare physician and outpatient hospital spending was on new technologies unavailable in the prior decade. Medical therapies are constantly being researched, so the difference between a therapy which is investigational versus standard of care is not always clear, particularly given cost-effectiveness considerations. Payers have utilization management clinical guidelines which do not pay for "experimental or investigational" therapies, or may require that
7930-404: The acute infection, notably new muscle weakness and extreme fatigue. This condition is known as post-polio syndrome (PPS) or post-polio sequelae. The symptoms of PPS are thought to involve a failure of the oversized motor units created during the recovery phase of the paralytic disease. Contributing factors that increase the risk of PPS include aging with loss of neuron units, the presence of
8052-430: The blood and lymphatics for long periods of time, sometimes as long as 17 weeks. In a small percentage of cases, it can spread and replicate in other sites, such as brown fat , the reticuloendothelial tissues, and muscle. This sustained replication causes a major viremia, and leads to the development of minor influenza-like symptoms. Rarely, this may progress and the virus may invade the central nervous system, provoking
8174-446: The body can compensate for residual paralysis in other ways. Weaker muscles can be used at a higher than usual intensity relative to the muscle's maximal capacity , little-used muscles can be developed, and ligaments can enable stability and mobility. Residual complications of paralytic polio often occur following the initial recovery process. Muscle paresis and paralysis can sometimes result in skeletal deformities, tightening of
8296-467: The brain tissue itself, can occur in rare cases, and is usually restricted to infants. It is characterized by confusion, changes in mental status, headaches, fever, and, less commonly, seizures and spastic paralysis . The term poliomyelitis derives from the Ancient Greek poliós ( πολιός ), meaning "grey", myelós ( µυελός "marrow"), referring to the grey matter of the spinal cord , and
8418-419: The cellular, molecular and physiological mechanisms of human health and disease. Pre-clinical research covers understanding of mechanisms that may lead to clinical research with people. Typically, the work requires no ethical approval, is supervised by scientists rather than physicians , and is carried out in a university or company, rather than a hospital. Clinical research is carried out with people as
8540-693: The color and appearance of the gray matter in the spinal column , causing it to appear reddish and swollen. Other destructive changes associated with paralytic disease occur in the forebrain region, specifically the hypothalamus and thalamus . Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, difficulty swallowing , muscle pain , loss of superficial and deep reflexes , paresthesia (pins and needles), irritability, constipation, or difficulty urinating. Paralysis generally develops one to ten days after early symptoms begin, progresses for two to three days, and
8662-402: The creation of rules and guidelines for the development of new medication, such as the guidelines for Good Clinical Practice (GCP). All ideas of regulation are based on a country's ethical standards code. This is why treatment of a particular disease in one country may not be allowed, but is in another. A major flaw and vulnerability in biomedical research appears to be the hypercompetition for
8784-491: The development of paralytic poliomyelitis, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS affected. The destruction of neuronal cells produces lesions within the spinal ganglia ; these may also occur in the reticular formation , vestibular nuclei , cerebellar vermis , and deep cerebellar nuclei . Inflammation associated with nerve cell destruction often alters
8906-415: The disease progresses to cause paralysis, this occurs within 7 to 21 days. Individuals who are exposed to the virus, either through infection or by immunization via polio vaccine , develop immunity . In immune individuals, IgA antibodies against poliovirus are present in the tonsils and gastrointestinal tract and able to block virus replication ; IgG and IgM antibodies against PV can prevent
9028-480: The early stages of the product development. According to Ariel Katz on average after a patent application is submitted it takes an additional 8 years before the FDA approves a drug for marketing. As such this would leave a company with only 12 years to market the drug to see a return on their investments. After a sharp decline of new drugs entering the US market following the 1962 Kefauver-Harris amendments economist Sam Petlzman concluded that cost of loss of innovation
9150-622: The effect on swallowing, secretions of mucus may build up in the airway, causing suffocation. Other signs and symptoms include facial weakness (caused by destruction of the trigeminal nerve and facial nerve , which innervate the cheeks, tear ducts , gums, and muscles of the face, among other structures), double vision , difficulty in chewing, and abnormal respiratory rate , depth, and rhythm (which may lead to respiratory arrest ). Pulmonary edema and shock are also possible and may be fatal. Approximately 19 percent of all paralytic polio cases have both bulbar and spinal symptoms; this subtype
9272-484: The establishment of the National Institutes of Health (NIH) in the mid-1940s, the main source of U.S. federal support of biomedical research, investment priorities and levels of funding have fluctuated. From 1995 to 2010, NIH support of biomedical research increased from 11 billion to 27 billion Despite the jump in federal spending, advancements measured by citations to publications and the number of drugs passed by
9394-418: The first time reporting regulations that were previously not required. The 2006 Federal Funding Accountability and Transparency Act mandates that all entities receiving over $ 25,000 in federal funds must report annual spending reports, including disclosure of executive salaries. The 2010 amendment to the act mandates that progress reports be submitted along with financial reporting. Data from the federal mandate
9516-495: The human body to heal and recover. Research focuses on developing effective treatments for a range of currently incurable diseases, such as cancer, arthritis and other musculoskeletal conditions, diabetes and cardiovascular diseases, as well as neurotrauma. In addition, ARMI is also looking at technologies to treat ageing itself via regeneration. Facilities at the Institute include FishCore, the largest zebrafish facility of its kind in
9638-427: The institute. Former groups include: Medical research Medical research encompasses a wide array of research, extending from " basic research " (also called bench science or bench research ), – involving fundamental scientific principles that may apply to a preclinical understanding – to clinical research , which involves studies of people who may be subjects in clinical trials . Within this spectrum
9760-400: The joints, and movement disability. Once the muscles in the limb become flaccid, they may interfere with the function of other muscles. A typical manifestation of this problem is equinus foot (similar to club foot ). This deformity develops when the muscles that pull the toes downward are working, but those that pull it upward are not, and the foot naturally tends to drop toward the ground. If
9882-472: The late 19th century in Europe and the United States , and in the 20th century, it became one of the most worrying childhood diseases . Following the introduction of polio vaccines in the 1950s, polio incidence declined rapidly. As of October 2023 , only Pakistan and Afghanistan remain endemic for wild poliovirus (WPV). Once infected, there is no specific treatment. The disease can be prevented by
10004-464: The legs, due to pooling of blood in paralyzed lower limbs. Complications from prolonged immobility involving the lungs , kidneys and heart include pulmonary edema , aspiration pneumonia , urinary tract infections , kidney stones , paralytic ileus , myocarditis and cor pulmonale . Between 25 percent and 50 percent of individuals who have recovered from paralytic polio in childhood can develop additional symptoms decades after recovering from
10126-459: The life of the interested companies' patents. Rules and regulations regarding conflict of interest disclosures are being studied by experts in the biomedical research field to eliminate conflicts of interest that could possibly affect the outcomes of biomedical research. Two laws which are both still in effect, one passed in 2006 and the other in 2010, were instrumental in defining funding reporting standards for biomedical research, and defining for
10248-409: The limb joins the body) than distally (the fingertips and toes ). Making up about two percent of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the bulbar region of the brain stem . The bulbar region is a white matter pathway that connects the cerebral cortex to the brain stem. The destruction of these nerves weakens the muscles supplied by
10370-408: The maintenance of government financial support levels through the era (the 0.7% four-year increase). Spending from industry-initiated research increased 25% (adjusted for inflation) over the same time period of time, from 2003 to 2007, an increase from $ 40 billion in 2003, to $ 58.6 billion in 2007. Industry sourced expenditures from 1994 to 2003 showed industry sponsored research funding increased 8.1%,
10492-471: The most prominent professional association for biomedical research companies, has recently begun to provide limited public funding reports. The earliest narrative describing a medical trial is found in the Book of Daniel , which says that Babylonian king Nebuchadnezzar ordered youths of royal blood to eat only red meat and wine for three years, while another group of youths ate only beans and water. The experiment
10614-482: The motor neurons of the anterior horn cells , or the ventral (front) grey matter section in the spinal column , which are responsible for movement of the muscles, including those of the trunk , limbs , and the intercostal muscles . Virus invasion causes inflammation of the nerve cells, leading to damage or destruction of motor neuron ganglia . When spinal neurons die, Wallerian degeneration takes place, leading to weakness of those muscles formerly innervated by
10736-417: The natural or "wild" poliovirus (WPV). Poliomyelitis is highly contagious. The disease is transmitted primarily via the fecal–oral route , by ingesting contaminated food or water. It is occasionally transmitted via the oral–oral route. It is seasonal in temperate climates , with peak transmission occurring in summer and autumn. These seasonal differences are far less pronounced in tropical areas. Polio
10858-478: The now-dead neurons. With the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles atrophy , becoming weak, floppy and poorly controlled, and finally completely paralyzed. Maximum paralysis progresses rapidly (two to four days), and usually involves fever and muscle pain. Deep tendon reflexes are also affected, and are typically absent or diminished; sensation (the ability to feel) in
10980-550: The paralysis of muscles used for breathing. The case fatality rate (CFR) varies by age: 2 to 5 percent of children and up to 15 to 30 percent of adults die. Bulbar polio often causes death if respiratory support is not provided; with support, its CFR ranges from 25 to 75 percent, depending on the age of the patient. When intermittent positive pressure ventilation is available, the fatalities can be reduced to 15 percent. Many cases of poliomyelitis result in only temporary paralysis. Generally in these cases, nerve impulses return to
11102-436: The paralyzed limbs, however, is not affected. The extent of spinal paralysis depends on the region of the cord affected, which may be cervical , thoracic , or lumbar . The virus may affect muscles on both sides of the body, but more often the paralysis is asymmetrical . Any limb or combination of limbs may be affected – one leg, one arm, or both legs and both arms. Paralysis is often more severe proximally (where
11224-407: The paralyzed muscle within a month, and recovery is complete in six to eight months. The neurophysiological processes involved in recovery following acute paralytic poliomyelitis are quite effective; muscles are able to retain normal strength even if half the original motor neurons have been lost. Paralysis remaining after one year is likely to be permanent, although some recovery of muscle strength
11346-558: The past century can be significantly attributed to advances resulting from medical research. Among the major benefits of medical research have been vaccines for measles and polio , insulin treatment for diabetes , classes of antibiotics for treating a host of maladies, medication for high blood pressure , improved treatments for AIDS , statins and other treatments for atherosclerosis , new surgical techniques such as microsurgery , and increasingly successful treatments for cancer . New, beneficial tests and treatments are expected as
11468-479: The patient to breathe without the support of a ventilator . It can lead to paralysis of the arms and legs and may also affect swallowing and heart functions. Paralytic poliomyelitis may be clinically suspected in individuals experiencing acute onset of flaccid paralysis in one or more limbs with decreased or absent tendon reflexes in the affected limbs that cannot be attributed to another apparent cause, and without sensory or cognitive loss. A laboratory diagnosis
11590-486: The problem is left untreated, the Achilles tendons at the back of the foot retract and the foot cannot take on a normal position. People with polio that develop equinus foot cannot walk properly because they cannot put their heels on the ground. A similar situation can develop if the arms become paralyzed. In some cases the growth of an affected leg is slowed by polio, while the other leg continues to grow normally. The result
11712-677: The recession, biomedical research spending decreased 2% in real terms in 2008. Despite an overall increase of investment in biomedical research, there has been stagnation, and in some areas a marked decline in the number of drug and device approvals over the same time period. As of 2010, industry sponsored research accounts for 58% of expenditures, NIH for 27% of expenditures, state governments for 5% of expenditures, non NIH-federal sources for 5% of expenditures and not-for-profit entities accounted for 4% of support. Federally funded biomedical research expenditures increased nominally, 0.7% (adjusted for inflation), from 2003 to 2007. Previous reports showed
11834-490: The remaining quarter are left with severe disability. The degree of both acute paralysis and residual paralysis is likely to be proportional to the degree of viremia , and inversely proportional to the degree of immunity . Spinal polio is rarely fatal. Without respiratory support, consequences of poliomyelitis with respiratory involvement include suffocation or pneumonia from aspiration of secretions . Overall, 5 to 10 percent of patients with paralytic polio die due to
11956-567: The resources and positions that are required to conduct science. The competition seems to suppress the creativity, cooperation, risk-taking, and original thinking required to make fundamental discoveries. Other consequences of today's highly pressured environment for research appear to be a substantial number of research publications whose results cannot be replicated, and perverse incentives in research funding that encourage grantee institutions to grow without making sufficient investments in their own faculty and facilities. Other risky trends include
12078-548: The spread of the virus to motor neurons of the central nervous system . Infection or vaccination with one serotype of poliovirus does not provide immunity against the other serotypes, and full immunity requires exposure to each serotype. A rare condition with a similar presentation, nonpoliovirus poliomyelitis, may result from infections with enteroviruses other than poliovirus. The oral polio vaccine, which has been in use since 1961, contains weakened viruses that can replicate. On rare occasions, these may be transmitted from
12200-495: The start of what is considered the "doubling period" of rapid NIH support. The second notable period started in 1997 and ended in 2010, a period where the NIH moved to organize research spending for engagement with the scientific community. Since 1980 the share of biomedical research funding from industry sources has grown from 32% to 62%, which has resulted in the development of numerous life-saving medical advances. The relationship between industry and government-funded research in
12322-510: The suffix -itis , which denotes inflammation , i.e., inflammation of the spinal cord's grey matter. The word was first used in 1874 and is attributed to the German physician Adolf Kussmaul . The first recorded use of the abbreviated version polio was in the Indianapolis Star in 1911. Poliomyelitis does not affect any species other than humans. The disease is caused by infection with
12444-426: The swing phase is initiated. With the help of an orthotic treatment with a stance phase control knee joint, a natural gait pattern can be achieved despite mechanical protection against unwanted knee flexion. In these cases, locked knee joints are often used, which have a good safety function, but do not allow knee flexion when walking during swing phase. With such joints, the knee joint remains mechanically blocked during
12566-430: The swing phase. Patients with locked knee joints must swing the leg forward with the knee extended even during the swing phase. This only works if the patient develops compensatory mechanisms, e.g. by raising the body's center of gravity in the swing phase (Duchenne limping) or by swinging the orthotic leg to the side (circumduction). Major polio epidemics were unknown before the 20th century; up until that time, polio
12688-410: The symptoms can be expected to persist for two to ten days, followed by complete recovery. In cases of spinal polio, if the affected nerve cells are completely destroyed, paralysis will be permanent; cells that are not destroyed, but lose function temporarily, may recover within four to six weeks after onset. Half the patients with spinal polio recover fully; one-quarter recover with mild disability, and
12810-420: The technology. Both government and industry research funding increased rapidly from between the years of 1994–2003; industry saw a compound average annual growth rate of 8.1% a year and slowed only slightly to a compound average annual growth rate of 5.8% from 2003 to 2008. " Conflict of interest " in the field of medical research has been defined as "a set of conditions in which professional judgment concerning
12932-498: The therapy is medically necessary or superior to cheaper treatments. For example, proton therapy was approved by the FDA, but private health insurers in the United States considered it unproven or unnecessary given its high cost, although it was ultimately covered for certain cancers. Fields of biomedical research include: Polio Poliomyelitis ( / ˌ p oʊ l i oʊ ˌ m aɪ ə ˈ l aɪ t ɪ s / POH -lee-oh- MY -ə- LY -tiss ), commonly shortened to polio ,
13054-411: The time of epiphyseal (growth) plate closure, the legs are more equal in length. Alternatively, a person can be fitted with custom-made footwear which corrects the difference in leg lengths. Other surgery to re-balance muscular agonist/antagonist imbalances may also be helpful. Extended use of braces or wheelchairs may cause compression neuropathy , as well as a loss of proper function of the veins in
13176-421: The tonsilar germinal centers ), the intestinal lymphoid tissue including the M cells of Peyer's patches , and the deep cervical and mesenteric lymph nodes , where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream. Known as viremia , the presence of a virus in the bloodstream enables it to be widely distributed throughout the body. Poliovirus can survive and multiply within
13298-519: The traditional OPV was able to revert to a virulent form. An improved oral vaccine with greater genetic stability (nOPV2) was developed and granted full licensure in December 2023. The term "poliomyelitis" is used to identify the disease caused by any of the three serotypes of poliovirus. Two basic patterns of polio infection are described: a minor illness that does not involve the central nervous system (CNS), sometimes called abortive poliomyelitis, and
13420-431: The vaccinated person to other people; in communities with good vaccine coverage , transmission is limited, and the virus dies out. In communities with low vaccine coverage, this weakened virus may continue to circulate and, over time may mutate and revert to a virulent form. Polio arising from this cause is referred to as circulating vaccine-derived poliovirus (cVDPV) or variant poliovirus in order to distinguish it from
13542-485: The virus can migrate from the gastrointestinal tract into the central nervous system (CNS). Most patients with CNS involvement develop nonparalytic aseptic meningitis , with symptoms of headache, neck, back, abdominal and extremity pain, fever, vomiting, stomach pain, lethargy , and irritability. About one to five in 1,000 cases progress to paralytic disease, in which the muscles become weak, floppy and poorly controlled, and, finally, completely paralyzed; this condition
13664-541: The virus in the feces or detecting antibodies against it in the blood. Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. The disease was first recognized as a distinct condition by the English physician Michael Underwood in 1789, and the virus that causes it was first identified in 1909 by the Austrian immunologist Karl Landsteiner . Major outbreaks started to occur in
13786-470: The world to combat polio: an inactivated poliovirus given by injection, and a weakened poliovirus given by mouth. Both types induce immunity to polio and are effective in protecting individuals from disease. The inactivated polio vaccine (IPV) was developed in 1952 by Jonas Salk at the University of Pittsburgh, and announced to the world on 12 April 1955. The Salk vaccine is based on poliovirus grown in
13908-417: The world to date and claims responsibility for numerous innovations that have improved global health. The historical funding of biomedical research has undergone many changes over the past century. Innovations such as the polio vaccine, antibiotics and antipsychotic agents, developed in the early years of the NIH lead to social and political support of the agency. Political initiatives in the early 1990s lead to
14030-413: Was an endemic disease worldwide. Mothers who had survived polio infection passed on temporary immunity to their babies in the womb and through breast milk. As a result, an infant who encountered a polio infection generally suffered only mild symptoms and acquired a long-term immunity to the disease. With improvements in sanitation and hygiene during the 19th century, the general level of herd immunity in
14152-467: Was created to support and regulate this curiosity. In 1945, Vannevar Bush said that biomedical scientific research was "the pacemaker of technological progress", an idea which contributed to the initiative to found the National Institutes of Health (NIH) in 1948, a historical benchmark that marked the beginning of a near century substantial investment in biomedical research. The NIH provides more financial support for medical research than any other agency in
14274-612: Was formally created in 1930 under the McNarey Mapes Amendment to oversee the regulation of Food and Drugs in the United States. In 1962 the Kefauver-Harris Amendments to the Food, Drug and Cosmetics Act made it so that before a drug was marketed in the United States the FDA must first approve that the drug was safe. The Kefauver-Harris amendments also mandated that more stringent clinical trials must be performed before
14396-518: Was granted emergency licencing in 2021, and subsequently full licensure in December 2023. This has greater genetic stability than the traditional oral vaccine and is less likely to revert to a virulent form. There is no cure for polio, but there are treatments. The focus of modern treatment has been on providing relief of symptoms, speeding recovery and preventing complications. Supportive measures include antibiotics to prevent infections in weakened muscles, analgesics for pain, moderate exercise and
14518-644: Was greater than the savings recognized by consumers no longer purchasing ineffective drugs. In 1984 the Hatch-Waxman Act or the Drug Price Competition and Patent Term Restoration Act of 1984 was passed by congress. The Hatch-Waxman Act was passed with the idea that giving brand manufacturers the ability to extend their patent by an additional 5 years would create greater incentives for innovation and private sector funding for investment. The relationship that exists with industry funded biomedical research
14640-424: Was intended to determine if a diet of vegetables and water was healthier than a diet of wine and red meat. At the experiment endpoint, the trial accomplished its prerogative: the youths who ate only beans and water were noticeably healthier. Scientific curiosity to understand health outcomes from varying treatments has been present for centuries, but it was not until the mid-19th century when an organizational platform
14762-640: Was selected, in competition with the live attenuated vaccines of Koprowski and other researchers, by the US National Institutes of Health. Licensed in 1962, it rapidly became the only oral polio vaccine used worldwide. OPV efficiently blocks person-to-person transmission of wild poliovirus by oral–oral and fecal–oral routes, thereby protecting both individual vaccine recipients and the wider community. The live attenuated virus may be transmitted from vaccinees to their unvaccinated contacts, resulting in wider community immunity. IPV confers good immunity but
14884-413: Was shown to be about 80 percent effective in preventing the development of paralytic poliomyelitis. It was also shown to reduce the severity of the disease in patients who developed polio. Due to the limited supply of blood plasma gamma globulin was later deemed impractical for widespread use and the medical community focused on the development of a polio vaccine. Two types of vaccine are used throughout
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